title: Identification of a critical region in the Drosophila ryanodine receptor that confers sensitivity to diamide insecticides.
abstract: Anthranilic diamides, which include the new commercial insecticide, chlorantraniliprole, are an exciting new class of chemistry that target insect ryanodine receptors. These receptors regulate release of stored intracellular calcium and play a critical role in muscle contraction. As with insects, nematodes express ryanodine receptors and are sensitive to the plant alkaloid, ryanodine. However the plant parasitic nematode, Meloidogyne incognita, is insensitive to anthranilic diamides. Expression of a full-length Drosophila melanogaster ryanodine receptor in an insect cell line confers sensitivity to the receptor agents, caffeine and ryanodine along with nanomolar sensitivity to anthranilic diamides. Replacement of a 46 amino acid segment in a highly divergent region of the Drosophila C-terminus with that from Meloidogyne results in a functional RyR which lack sensitivity to diamide insecticides. These findings indicate that this region is critical to diamide sensitivity in insect ryanodine receptors. Furthermore, this region may contribute to our understanding of the differential selectivity diamides exhibit for insect over mammalian ryanodine receptors.
authors.affiliation: Department of Microbiology and Biotechnology, Institute of Microbiology, Chinese Academy of Sciences, 1 West Beichen Road, Chaoyang District, Beijing 100101, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tao
authors.forename: Steven
authors.initials: S
authors.lastname: Gutteridge
authors.forename: Eric A
authors.initials: EA
authors.lastname: Benner
authors.forename: Lihong
authors.initials: L
authors.lastname: Wu
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Rhoades
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Sacher
authors.forename: Michel A
authors.initials: MA
authors.lastname: Rivera
authors.forename: Johan
authors.initials: J
authors.lastname: Desaeger
authors.forename: Daniel
authors.initials: D
authors.lastname: Cordova
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003958:Diamide / Q000633:toxicity*; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D008969:Molecular Sequence Data; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014431:Tylenchoidea / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D015801:Helminth Proteins; D007306:Insecticides; D019837:Ryanodine Receptor Calcium Release Channel; D003958:Diamide
keywords: Chlorantraniliprole; Cyantraniliprole; Cyazypyr™; Flubendiamide; Nematode; Rynaxypyr®